LIVER ALCOHOL AND ALDEHYDE DEHYDROGENASE: INHIBITION AND POTENTIATION BY HISTAMINE AGONISTS AND ANTAGONISTS |
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| Authors: | F S Messiha M J Hughes |
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| Institution: | Psychopharmacology Laboratory, Departments of Pathology, Psychiatry and Department of Physiology, Texas Tech University School of Medicine, Lubbock, Texas, U.S.A. |
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| Abstract: | 1. The in vitro effects of histamine, some other Hi- and H2-receptor agonists and some antagonists were studied on the specific activities and kinetics of rat liver alcohol dehydrogenase (ADH), and cytoplasmic and mitochondrial liver aldehyde dehydrogenase (ALDH). 2. Histamine (H1- and H2-agonist) non-competitively inhibited ADH and ALDH, 2-(2-aminoethyl) pyridine (Hi-receptor agonist) non-competitively inhibited ADH. There were no changes of cytoplasmic and mitochondrial liver ALDH activities in the presence of 2-(2-aminoethyl) pyridine. 3. Betazole (H2-receptor agonist) produced a competitive inhibition of mitochondrial ALDH but not of ADH or cytoplasmic ALDH. 4. Diphenhydramine (H1-receptor antagonist) non-competitively inhibited ADH at a lower concentration. It stimulated mitochondrial ALDH activity without changes in cytoplasmic ALDH from control values. 5. Burimamide (H2-receptor antagonist) produced a biphasic and dose-dependent stimulation and non-competitive inhibition of ADH and it non-competitively inhibited ALDH in both cytoplasmic and mitochondrial fractions. Metiamide (H2-receptor antagonist) non-competitively inhibited all ADH and ALDH of both liver fraction studied. 6. It is concluded that liver ADH and ALDH activity can be altered by compounds which affect both Hi- and H2-histamine receptors and that these compounds may cause an in vivo potentiation and/or reduction of the toxic effect of ethanol. |
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| Keywords: | betazole burimamide diphenhydramine H1-and H2-receptor agonists H1- and H2-receptor antagonists histamine liver alcohol dehydrogenase liver aldehyde dehydrogenase metiamide toxic effect of ethanol |
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